Development and Validation of the Facial Line Distress Scale for Lateral Canthal Lines: FINE-LCL.

Background: Currently available patient-reported outcome measures (PROM) have limited ability to assess unique issues related to lateral canthal lines (LCL). This study aimed to develop a PROM to assess the severity and psychosocial impact of LCL in afflicted patients. Methods: We conducted a cross-sectional survey at a tertiary hospital and two local clinics in Korea. Exploratory factor analysis was conducted to identify the underlying factor structure of the Facial Line Distress Scale for LCL (FINE-LCL), and the internal consistency and test-retest reliability were also examined. Results: We developed a questionnaire comprising 20 items in four domains. Coefficient alphas ranged from 0.94 to 0.97 for subdomains and 0.97 for the total questionnaire. The test-retest intraclass correlation coefficient ranged from 0.77 to 0.90. The FINE-LCL was moderately correlated with the appearance appraisal score and body image. Analysis of the accuracy of the FINE-LCL score in predicting severe LCL was characterized by an area under the curve of 0.79. Conclusions: FINE-LCL is a reliable, valid, and comprehensive PROM for the assessment of the severity of LCL and their associated distress.

Development and Validation of Facial Line Distress Scale for Forehead Lines: FINE-FL.

BACKGROUND: Forehead lines (FL) are one of the main signs of aging. Traditional tools to measure FL have limited ability to evaluate the multidimensional impact of these lines on appearance, confidence, and psychological and social relationships. OBJECTIVES: We developed and validated the Facial Line Distress Scale-Forehead Lines (FINE-FL) to evaluate the severity and psychosocial distress associated with FL. METHODS: We conducted a cross-sectional survey for FINE-FL psychometric validation at a tertiary hospital and 2 local clinics in Korea. First, a preliminary item pool for the FINE-FL was developed through a qualitative interview based on literature reviews and expert consultations. Second, cognitive interviews and a pilot test were conducted to evaluate comprehension, ease of response, acceptability of terminology, phrasing, and response options. FINE-FL consisted of 26 items. In this study, exploratory factor analysis was conducted to identify the underlying factor structure of the FINE-FL, and internal consistency and test-retest reliability were also examined. RESULTS: We found 21 items in 4 domains. The model fit was good. Coefficient αs ranged from 0.89 to 0.95 for subdomains and 0.96 for the total. The FINE-FL was moderately correlated with the appearance appraisal score. On the test-retest, the range of the intraclass correlation coefficient was 0.65 to 0.79. CONCLUSIONS: FINE-FL is a reliable, valid, and comprehensive patient-reported outcome measure for assessing FL severity and distress. This will be helpful in determining a patient's eligibility for inclusion in a study and measuring primary or secondary effectiveness endpoints for forehead line treatment.

Regulation of nicotinic acetylcholine receptor turnover by MuRF1 connects muscle activity to endo/lysosomal and atrophy pathways.

Muscle atrophy is a process of muscle wasting induced under a series of catabolic stress conditions, such as denervation, disuse, cancer cachexia, heart and renal failure, AIDS, and aging. Neuromuscular junctions (NMJs), the synapses between motor neurons and muscle fibers undergo major changes in atrophying muscles, ranging from mild morphological alterations to complete disintegration. In this study, we hypothesized that remodeling of NMJs and muscle atrophy could be linked together. To test this, we examined if a major atrophy-promoting E3 ubiquitin ligase, MuRF1, is involved in the maintenance of NMJs. Immunofluorescence revealed that MuRF1 is highly enriched close to the NMJ. Affinity precipitation and in vivo imaging showed that MuRF1 interacts in endocytic structures with both, acetylcholine receptor, the primary postsynaptic protein of the NMJ, as well as with Bif-1, an autophagy- and endocytosis-regulating factor. In vivo imaging, radio labeling, and weighing approaches demonstrated that metabolic destabilization of acetylcholine receptors and muscle atrophy induced by denervation were significantly rescued in MuRF1-KO animals. Notably, interaction with Bif-1, and the rescue of AChR lifetime and muscle atrophy were specific to MuRF1 but not MuRF2. Our data demonstrate an involvement of MuRF1 in membrane protein-turnover, including the degradation of AChRs at the NMJ under atrophying conditions where MuRF1 also interacts and associates with Bif-1.

Rapsyn mediates subsynaptic anchoring of PKA type I and stabilisation of acetylcholine receptor in vivo.

The stabilisation of acetylcholine receptors (AChRs) at the neuromuscular junction depends on muscle activity and the cooperative action of myosin Va and protein kinase A (PKA) type I. To execute its function, PKA has to be present in a subsynaptic microdomain where it is enriched by anchoring proteins. Here, we show that the AChR-associated protein, rapsyn, interacts with PKA type I in C2C12 and T-REx293 cells as well as in live mouse muscle beneath the neuromuscular junction. Molecular modelling, immunoprecipitation and bimolecular fluorescence complementation approaches identify an α-helical stretch of rapsyn to be crucial for binding to the dimerisation and docking domain of PKA type I. When expressed in live mouse muscle, a peptide encompassing the rapsyn α-helical sequence efficiently delocalises PKA type I from the neuromuscular junction. The same peptide, as well as a rapsyn construct lacking the α-helical domain, induces severe alteration of acetylcholine receptor turnover as well as fragmentation of synapses. This shows that rapsyn anchors PKA type I in close proximity to the postsynaptic membrane and suggests that this function is essential for synapse maintenance.